Two areas of research on hormonal control of adipocyte metabolism are summarized: (A) Previously, we reported the discovery of perilipin, an adipocyte-specific protein that is associated with the lipid storage droplet and multiply phosphorylated upon elevation of cAMP. We now have obtained cDNAs that contain the entire predicted coding sequences for major (57 kDa) and minor (46 kDa) forms of perilipin, A and B, respectively. The two forms appear to arise from alternative splicing, and both proteins are found in rat adipocytes in tight association with the lipid storage droplet. Total blockade of triacylglycerol synthesis does not interfere with perilipin expression, suggesting that nascent lipid droplets, the lipid packaging moieties, arise independent of lipid synthesis. Confocal microscopy combined with immunofluorescence with anti-perilipin antibodies reveals that lipolytic stimulation of cultured 3T3-L1 adipocytes leads to a massive structural change in the lipid storage droplet surface. Such data indicate that the lipid droplet is an active participant in lipolysis, i.e., activation of the rate-limiting enzyme, hormone-sensitive lipase, is but one of several concerted reactions required to mobilize the stored lipid. (B) Previously, we found that Interleukin-6 (IL-6) acts directly on adipoblasts to inhibit their differentiation into adipocytes and on adipocytes to inhibit lipoprotein lipase activity, data that suggest a role for this cytokine in cachexia. Similarly, tumor necrosis factor (TNF/cachectin), another factor implicated in cachexia, acts directly on adipocytes to stimulate IL-6 production. A comparison of the effects of IL-6 and TNF in radiophosphate-loaded 3T3-L1 adipocytes by autoradiography of 2D gels reveals that the cytokines stimulate the phosphorylation of different proteins. Similarly, IL-6 stimulates the tyrosine phosphorylation of 4 different proteins, only one of which is modified by TNF. These data indicate that the two cytokines act by different signalling mechanism and suggest that tyrosine kinase activation may mediate some IL-6 effects.